Multi-center, Open-label, Phase 1b Study in Patients With Relapsed/Refractory Multiple Myeloma (RRMM)

NCT04045795 | Completed Phase 1 FDA Drug FDA Device

• 3 other identifiers: TCD15484U1111-1211-95252018-001996-19
• Study Type: interventional
• Target: 56
• Locations: 6 countries
• Sites: 14

Brief Summary

Primary Objectives:

• To evaluate the safety and tolerability of isatuximab administered subcutaneously (SC) versus intravenously (IV)
• To assess the safety and tolerability (including local injection site tolerability) of isatuximab using the (investigational) isatuximab injector device
• To evaluate the pharmacokinetics (PK) of SC and IV isatuximab Secondary Objectives:
• To estimate absolute bioavailability of SC and IV isatuximab
• To measure receptor occupancy (RO) after isatuximab SC versus IV administration
• To assess efficacy of isatuximab after SC and IV administration
• To assess patient expectations prior to and patient experience and satisfaction after SC administration
• To evaluate potential immunogenicity of SC or IV isatuximab

Conditions

Multiple Myeloma

Keywords

Anti-CD38 monoclonal antibody

Outcome Measures

Primary Outcomes (9)

• Assessment of adverse events (AEs)

  Number of participants with adverse events

  Baseline to 30 days after last study treatment administration (up to approximately 14 months after first study treatment administration)

• Pharmacokinetic (PK) assessment: Ceoi

  Concentration observed at the end of infusion (Ceoi)

  Baseline to end of treatment (EOT) after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)

• PK assessment: Cmax

  Maximum concentration observed after the first infusion (Cmax)

  Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)

• PK assessment: tmax

  Time to reach Cmax (tmax)

  Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)

• PK assessment: Clast

  Last concentration observed above the lower limit of quantification after the first infusion (Clast)

  Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)

• PK assessment: tlast

  Time of Clast (tlast)

  Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)

• PK assessment: Ctrough

  Concentration observed just before treatment administration during repeated dosing (Ctrough)

  Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)

• PK assessment: AUClast

  Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to time of the last concentration observed above the lower limit of quantification (ie, Clast) (AUClast)

  Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)

• PK assessment: AUC0 T

  Area under the plasma concentration versus time curve calculated over the dosing interval T (168h or 336h) (AUC0 T)

  Baseline to EOT after isatuximab SC and to Cycle 10 after IV (28 days per Cycle)

Secondary Outcomes (11)

• Estimation of absolute bioavailability of isatuximab

  Day 8

• Overall response rate (ORR)

  From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)

• Duration of response (DOR)

  From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)

• Time to response (TTR)

  From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)

• Time to progression (TTP)

  From day -21 to day 60 after last study treatment (up to approximately 14 months after first study treatment administration)

Study Arms (5)

Dose regimen 1

EXPERIMENTAL

Isatuximab SC administration dose level 1 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle

Drug: pomalidomide; Drug: dexamethasone; Drug: isatuximab SAR650984 SC

Dose regimen 2

EXPERIMENTAL

Isatuximab SC administration dose level 2 once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle

Drug: pomalidomide; Drug: dexamethasone; Drug: isatuximab SAR650984 SC

Dose regimen 3

EXPERIMENTAL

Isatuximab SC administration dose level 3 using the investigational injector device once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle

Drug: pomalidomide; Drug: dexamethasone; Drug: isatuximab SAR650984 SC; Device: Investigational injector device

Dose regimen 4

EXPERIMENTAL

Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle

Drug: isatuximab SAR650984 IV; Drug: pomalidomide; Drug: dexamethasone

Dose regimen 5

EXPERIMENTAL

Isatuximab IV administration once weekly for 4 weeks (Cycle 1) and on Day 1 and Day 15 of each subsequent cycle

Drug: isatuximab SAR650984 IV; Drug: pomalidomide; Drug: dexamethasone

Interventions

isatuximab SAR650984 IV DRUG

Pharmaceutical form: solution Route of administration: intravenous

Also known as: Sarclisa

Dose regimen 4; Dose regimen 5

pomalidomide DRUG

Pharmaceutical form: tablet Route of administration: oral

Also known as: Pomalyst®

Dose regimen 1; Dose regimen 2; Dose regimen 3; Dose regimen 4; Dose regimen 5

dexamethasone DRUG

Pharmaceutical form: tablet Route of administration: oral

Also known as: Decadron®

Dose regimen 1; Dose regimen 2; Dose regimen 3; Dose regimen 4; Dose regimen 5

isatuximab SAR650984 SC DRUG

Pharmaceutical form: solution Route of administration: subcutaneous

Dose regimen 1; Dose regimen 2; Dose regimen 3

Investigational injector device DEVICE

Subcutaneous administration

Dose regimen 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
• Participant must be above 18 years of age or country's legal age of majority if the legal age is \>18 years old, at the time of signing the informed consent.
• Participant has been previously diagnosed with multiple myeloma (MM) based on standard criteria and currently requires treatment because MM has relapsed following a response, according to International Myeloma Working Group (IMWG) criteria.
• Participant has received at least two previous therapies including lenalidomide and a proteasome inhibitor and has demonstrated disease progression on last therapy or after completion of the last therapy.
• Participants with measurable disease defined as at least one of the following:
• Serum M protein ≥ 0.5 g/dL (≥5 g/L).
• Urine M protein ≥ 200 mg/24 hours.
• Serum free light chain (FLC) assay: Involved FLC assay ≥ 10 mg/dL (≥ 100 mg/L) and an abnormal serum FLC ratio (\<0.26 or \>1.65).
• Male or female: Contraceptive use by men or women

You may not qualify if:

• Malignancy within 3 years prior to enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status score \>2.
• Inadequate hematological, liver or renal function.
• Serum calcium (corrected for albumin) level above the upper limit of normal (ULN) range.
• Patients with prior anti-CD38 treatment are excluded if:
• Refractory to anti-CD38 treatment defined as progression on or within 60 days of the last dose of the anti-CD38 or,
• Intolerant to the anti-CD38 previously received or,
• Progression after initial response on anti-CD38 therapy with a washout period inferior to 9 months before the first dose of isatuximab SC or IV.
• Participant did not achieve a minimal response or better to at least one of the previous lines of treatment (ie, primary refractory disease is not eligible).
• Received any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer.
• Prior anti-cancer therapy within 14 days.
• Any \>Grade 1 adverse reaction unresolved from previous treatments according to the NCI-CTCAE v5.0. The presence of alopecia or peripheral neuropathy ≤ Grade 2 without pain is allowed.
• Daily requirement for corticosteroids.
• Known to be HIV+ or to have hepatitis A or uncontrolled or active hepatitis B virus (HBV) infection (patients with positive HBsAg \[HBsAg\] and/or HBV DNA) or active HCV (HCV) infection (positive HCV RNA and negative anti-HCV).
• Active tuberculosis and severe infections requiring treatment with antibiotic parenteral administration.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (14)

~Banner MD Anderson Cancer Center Site Number : 8400005

Gilbert, Arizona, 85234, United States

Location

City of Hope Site Number : 8400002

Duarte, California, 91010, United States

Location

Gabrail Cancer Center Site Number : 8400001

Canton, Ohio, 44718, United States

Location

Investigational Site Number : 0360002

Blacktown, New South Wales, 2148, Australia

Location

Investigational Site Number : 0360001

Wollongong, New South Wales, 2500, Australia

Location

Investigational Site Number : 0360004

Fitzroy, Victoria, 3065, Australia

Location

Investigational Site Number : 0360003

Richmond, Victoria, 3121, Australia

Location

Investigational Site Number : 0560001

Leuven, 3000, Belgium

Location

Investigational Site Number : 2500001

Nantes, 44093, France

Location

Investigational Site Number : 2500002

Toulouse, 31059, France

Location

Investigational Site Number : 3920002

Okayama, Okayama-ken, 701-1192, Japan

Location

Investigational Site Number : 3920001

Shibuya-ku, Tokyo, 150-8935, Japan

Location

Investigational Site Number : 7240002

Santander, Cantabria, 39008, Spain

Location

Investigational Site Number : 7240001

Badalona, Catalunya [Cataluña], 08916, Spain

Location

Related Links

• TCD15484 Plain Language Results Summary

MeSH Terms

Conditions

Multiple Myeloma

Interventions

isatuximab; pomalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2019
• First Posted: August 6, 2019
• Study Start: August 6, 2019
• Primary Completion: March 27, 2024
• Study Completion: March 27, 2024
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (3); BE (1); AU (4); FR (2); JP (2); ES (2)